A spectrum of retinal vasculature measures and coronary artery disease

Background and aims We aimed to comprehensively describe a spectrum of retinal vessel measures including fractal dimension (Df) and their associations with indices of coronary artery disease (CAD) extent and severity, as well as hypertension and diabetes. Methods The Australian Heart Eye Study (AHES) is an observational study that surveyed 1680 participants presenting to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. A range of newer retinal vessel geometric measures (Df, curvature tortuosity, and branching angle) were quantified from retinal photographs using semi-automated software, the Singapore ‘I’ Vessel Assessment (SIVA) tool. A combined retinal score was constructed, aiming to assess the joint effect of multiple retinal vessel parameters on CAD, comprising of those variables that were most strongly significant in multivariate analysis - Df, arteriolar curvature tortuosity, and retinal arteriolar calibre. CAD was objectively quantified using a range of measures obtained from coronary angiography. Results A total of 1187 participants had complete data on retinal vessel measurements and coronary vessel evaluation. Retinal vascular Df and curvature tortuosity decreased with increasing age; women had significantly lower Df than men (p<0.003). Straighter retinal vessels were associated with CAD extent and Gensini scores in multivariable analysis (p<0.02). Accounting for media opacity by sub-group analysis in pseudophakic patients, the combined retinal score was associated with stenosis greater than 50% in any coronary artery segment (vessel score) and obstructive coronary stenosis in all three main coronary arteries (segment score) (p = 0.01). Lower Df and narrower arteriolar branching angle were associated with CAD vessel score (p<0.03). In sex-stratified multivariate analyses, straighter arterioles were associated with greater odds of CAD in men, and narrower venular branching angle was associated with CAD in women. Conclusions A range of retinal vessel measures were associated with CAD extent and severity. A sparser retinal microvascular network (smaller Df) was associated with older age and female gender. After accounting for the impact of media opacity, retinal vessel measures were associated with more diffuse and severe CAD.